Formulation for treating chronic wounds

ABSTRACT

Inventive subject matter disclosed herein includes a method for treating a chronic wound, and methods for treating bacterial infections. The method for treating a chronic wound includes mechanically debriding a chronic wound, and applying a formulation to the wound for 5 to 60 seconds, the formulation including: phenolsulfonic acid—37% by weight; guaiacolsulfonic acid—24% by weight; free sulfuric acid—29% by weight; and water—10% by weight.

CROSS-REFERENCE TO RELATED APPLICATION

The present application claims the benefit of U.S. provisionalapplication Ser. No. 62/044,650, filed Sep. 2, 2014, the disclosure ofwhich is incorporated by reference herein.

FIELD

Inventive subject matter disclosed herein relates to formulation andmethod embodiments for treating chronic wounds and for preventing andtreating bacterial infections.

BACKGROUND

Wounds, such as chronic wounds that do not heal, pose a vexing problemfor patients and health professionals. These wounds include, but are notlimited to chronic venous leg ulcers, pressure ulcers, diabetic ulcers,decubitus ulcers, stasis ulcers, dermal ulcers, burns, and pressureulcers. Chronic wounds are characterized by necrotic tissue that delayshealing. Necrotic tissue may act as a reservoir for bacterial growth.Necrotic tissue also contains inflammatory mediators that promoteinflammation and impair cellular migration.

Conventional treatment for chronic wounds includes debridement thatattempts to remove the necrotic tissue. Debridement may be autolytic,enzymatic, mechanical, surgical, and, in some instances, performed withmaggots. None of these conventional debridement treatments has beensuccessful in healing chronic wounds.

DESCRIPTION OF DRAWINGS

FIG. 1 is a top plan view of a chronic wound prior to treatment.

FIG. 2 is a top plan view of the chronic wound of FIG. 1 one week aftera treatment, using a formulation embodiment of the present invention.

FIG. 3 is a top plan view of the chronic wound of FIG. 1 two weeks aftera treatment, using the formulation embodiment of the present inventionused in FIG. 2.

FIG. 4 is a top plan view the chronic wound of FIG. 1 three weeks aftera treatment, using the formulation embodiment of the present inventionused in FIG. 2. The chronic wound is healed.

SUMMARY

One embodiment of the present invention is a liquid formulation fortreating chronic wounds. The liquid formulation includes the following:

phenolsulfonic acid—37% by weight;

guaiacolsulfonic acid—24% by weight;

free sulfuric acid—29% by weight; and

water—10% by weight

Another embodiment includes a gel formulation for treating chronicwounds. The gel formulation includes the following:

phenolsulfonic acid—36% by weight;

guaiacolsulfonic acid—23% by weight;

free sulfuric acid—28% by weight;

water—10% by weight; and

colloidal silica—3% by weight.

Another embodiment includes a liquid formulation for treating chronicwounds. The embodiment includes the following:

benzenesulfonic acid 45% by weight;

phenolsulfonic acid—40% by weight; and

water—15% by weight.

Another embodiment includes a gel formulation for treating chronicwounds. The gel includes the following:

benzenesulfonic acid—43% by weight;

phenolsulfonic acid—38% by weight;

water—14% by weight; and

colloidal silica—5% by weight.

Another embodiment includes a liquid formulation for treating chronicwounds. The formulation includes the following components andconcentration ranges:

phenolsufonic acid (10-75% wt. percent);

guaiacolsulfonic acid (10-75% wt. percent);

free sulfuric acid (0-30% wt. percent);

water (0-30% wt. percent); and

colloidal silica (0-10% wt. percent).

Another formulation embodiment for treating chronic wounds, includes thefollowing components and concentration ranges:

benzenesulfonic acid (10-75% by weight);

phenolsulfonic acid (10-75% by weight);

water (0-30% by weight); and

colloidal silica (0-10% by weight).

Another embodiment is a method of treating a chronic wound, thatincludes:

applying a formulation to the wound for 5 to 60 seconds, the formulationcomprising:

-   -   phenolsulfonic acid—37% by weight; guaiacolsulfonic acid—24% by        weight; free sulfuric acid—29% by weight; and water—10% by        weight.

Another embodiment is a method for treating a chronic wound, thatincludes:

applying a formulation to the wound for 5 to 60 seconds, the formulationcomprising: gel formulation for treating chronic wounds, that includes:

-   -   phenolsulfonic acid—36% by weight;    -   guaiacolsulfonic acid—23% by weight;    -   free sulfuric acid—28% by weight;    -   water—10% by weight; and    -   colloidal silica—3% by weight.

Another embodiment includes a method of treating a chronic wound, thatincludes:

applying a formulation to the wound for 5 to 60 seconds, the formulationcomprising: A liquid formulation for treating chronic wounds, thatincludes:

-   -   benzenesulfonic acid 45% by weight;    -   phenolsulfonic acid—40% by weight; and    -   water—15% by weight.

Another embodiment includes a method of treating a chronic wound, thatincludes:

applying a formulation to the wound for 5 to 60 seconds, the formulationcomprising:

-   -   a gel formulation for treating chronic wounds, that includes:        -   benzenesulfonic acid—43% by weight;        -   phenolsulfonic acid—38% by weight;        -   water—14% by weight; and        -   colloidal silica—5% by weight.

Another embodiment includes a method of treating a chronic wound, thatincludes:

applying a formulation to the wound for 5 to 60 seconds, the formulationthat includes:

-   -   a liquid formulation for treating chronic wounds, that includes:        -   phenolsufonic acid (10-75% wt. percent);        -   guaiacolsulfonic acid (10-75% wt. percent);        -   free sulfuric acid (0-30% wt percent);        -   water (0-30% wt. percent); and        -   colloidalsSilica (0-10% wt. percent).

Another embodiment includes a method of treating a chronic wound,including:

-   -   applying a formulation to the wound for 5 to 60 seconds, the        formulation comprising:    -   a formulation for treating chronic wounds, including:        -   benzenesulfonic acid (10-75% wt. percent);        -   phenolsulfonic acid (10-75% wt. percent);        -   water (0-30% wt. percent); and        -   colloidal Silica (0-10% wt. percent).

Another embodiment includes a method of treating a chronic wound,including: applying a formulation to the wound for 5 to 60 seconds, theformulation comprising:

phenolsulfonic acid 25-80% by weight;

guaiacolsulfonic acid 25-80% by weight:

ammonium phenolsulfonate 0-5% by weight; and

water 13-30% by weight.

Another embodiment includes a method for preventing infections byantibiotic resistant bacteria, including: applying a formulationcomprising phenolsulfonic acid in a concentration of 10-75% by weight;guiacolfonic acid in a concentration of 10-30% by weight; free sulfuricacid in a concentration of 0-30% by weight; water in a concentration of0-30% by weight; and colloidal silica in a concentration of 0 to 10% byweight topically to a surface of a living being.

Another embodiment includes a method for preventing bacterialinfections, including: applying a formulation comprising phenolsulfonicacid in a concentration of 10-75% by weight; guiacolfonic acid in aconcentration of 10-30% by weight; free sulfuric acid in a concentrationof 0-30% by weight; water in a concentration of 0-30% by weight; andcolloidal silica by weight topically to a surface of a living being.

Another method embodiment for preventing bacterial infections bypersistent bacteria, including: applying a formulation comprisingphenolsulfonic acid in a concentration of 10-75% by weight; guiacolfonicacid in a concentration of 10-30% by weight; free sulfuric acid in aconcentration of 0-30% by weight; water in a concentration of 0-30% byweight; and colloidal silica by weight topically to a surface of aliving being.

Another method embodiment for preventing biofilm formation, includes:applying a formulation comprising phenolsulfonic acid in a concentrationof 10-75% by weight; guiacolfonic acid in a concentration of 10-30% byweight; free sulfuric acid in a concentration of 0-30% by weight; waterin a concentration of 0-30% by weight; and colloidal silica by weighttopically to a surface of a living being.

Another method embodiment for treating infections by antibioticresistant bacteria, includes: applying a formulation comprisingphenolsulfonic acid in a concentration of 10-75% by weight; guiacolfonicacid in a concentration of 0-30% by weight; free sulfuric acid in aconcentration of 10-30% by weight; water in a concentration of 0-30% byweight; and colloidal silica in a concentration of 0 to 10% by weighttopically to a surface of a living being infected with antibioticresistant bacteria.

Another method embodiment for treating bacterial infections, includes:applying a formulation comprising phenolsulfonic acid in a concentrationof 0-75% by weight; guiacolfonic acid in a concentration of 10-30% byweight; free sulfuric acid in a concentration of 10-30% by weight; waterin a concentration of 0-30% by weight; and colloidal silica by weighttopically to a surface of a living being infected with a bacterialinfection.

Another method embodiment for treating bacterial infections, caused bybacteria in a persistent state includes: applying a formulationcomprising phenolsulfonic acid in a concentration of 10-75% by weight;guiacolfonic acid in a concentration of 10-30% by weight; free sulfuricacid in a concentration of 0-30% by weight; water in a concentration of0-30% by weight; and colloidal silica by weight topically to a surfaceof a living being infected by bacteria in a persistent state.

Another method embodiment for treating biofilm infections, includes:applying a formulation comprising phenolsulfonic acid in a concentrationof 10-75% by weight; guiacolfonic acid in a concentration of 10-30% byweight; free sulfuric acid in a concentration of 0-30% by weight; waterin a concentration of 0-30% by weight; and colloidal silica in aconcentration of 0 to 10% by weight topically to a surface of a livingbeing contaminated by biofilm.

DETAILED DESCRIPTION

Embodiments of the invention are described in sufficient detail toenable those skilled in the art to practice the invention. Otherembodiments may be utilized and structural, logical, chemical, and otherchanges may be made without departing from the spirit or scope of theinvention discussed herein. The following detailed description is,therefore, not to be taken in a limiting sense, and the scope of theinvention discussed herein is defined only by the appended claims.

Formulation embodiments disclosed herein are used as an adjunctive agentto all other forms of debridement and are compatible with all otherforms of debridement. For one embodiment, the formulation embodimentsare used as an adjunctive rinse following surgical debridement, alsoknown as sharp debridement, which is a conventional form of mechanicaldebridement used in the treatment of chronic wounds.

Formulation embodiments include liquid and gel embodiments that, whenapplied to a chronic wound, effectively reduce the size of the woundand, in some instances, heal the chronic wound. It is believed that theformulations disclosed herein work by debriding the wound and bydestroying biofilms and bacteria on and in a skin wound and desiccatingand washing away necrotic tissue defining the chronic wound. Themechanism of action is believed to be the following: Application of aformulation embodiment disclosed herein acts as both a mechanicaldebridement and a chemical debridement. The mechanical debridementaction derives from an elevated viscosity and density of the formulationthat allows the formulation to deliver a higher level of mechanicalpressure and shear stress across a surface. The chemical debridementderives from a desiccating action of the formulation embodiment whichacts to destabilize the cohesion of necrotized tissues and microbialbiofilm so that they are easily carried away by the mechanical action.

Formulation embodiments not only absorb water mechanically, i.e. absorbwater that is adhered to microbes and biofilm within and proximal to awound, but also absorb water that is electrostatically bonded, i.e.hydrogen bonded, with structural components of bacteria and othermicrobes in wounds, thereby desiccating bacterial structure anddestroying bacterial structural integrity. Formulation embodiments alsodesiccate any residual necrotic tissue.

The mechanism of action is such that formulation embodiments do not justabsorb bound water, but also absorb water that is electrostaticallybonded, i.e. hydrogen bonded, with water from the structural componentsof bacteria, thereby destroying bacterial integrity. Additionally,formulation embodiments prevent a destructive immune response initiatedby necrotizing tissue by eliminating the necrotizing tissue. Eliminationprevents the body from initiating an inflammatory immune response.

Method embodiments disclosed herein are useful against bacteria,biofilm, prions, antibiotic resistant bacteria and persistent bacteria.One method embodiment for preventing infections by antibiotic resistantbacteria includes applying a formulation that includes phenolsulfonicacid in a concentration of 10-75% by weight; Guiacolfonic acid in aconcentration of 10-30% by weight; free sulfuric acid in a concentrationof 0-30% by weight; water in a concentration of 0-30% by weight; andcolloidal silica in a concentration of 0 to 10% by weight topically tobroken skin or bone or an organ surface that is at risk for infection.This method is also used in treating and killing bacteria, biofilm,prions, antibiotic resistant bacteria and persistent bacteria. Allformulation embodiments disclosed herein are applicable as a spray, gelor as a solid with time release.

Another method embodiment for preventing bacterial infections includesapplying a formulation that includes phenolsulfonic acid in aconcentration of 10-75% by weight; guiacolfonic acid in a concentrationof 10-30% by weight; free sulfuric acid in a concentration of 0-30% byweight; water in a concentration of 0-30% by weight; and colloidalsilica by weight topically to contaminated bone.

Another method embodiment for preventing bacterial infections, includesapplying a formulation that includes phenolsulfonic acid in aconcentration of 10-75% by weight; guiacolfonic acid in a concentrationof 10-30% by weight; free sulfuric acid in a concentration of 0-30% byweight; water in a concentration of 0-30% by weight; and colloidalsilica by weight topically to a surface of a contaminated organ.

Embodiments disclosed herein are also useful against bacteria that arein a persistent state; that is bacteria that have never been cultured ina lab.

Embodiments are also useful in preventing bacterial infections in anorgan.

Once structural integrity of a biofilm is destroyed by exposure to aformulation disclosed herein, the microbes die and the biofilm isdisrupted. Bacteria, and other pathogens exposed to formulationembodiments disclosed herein do not develop a resistance to theformulations. Formulation and method embodiments disclosed herein areeffective against all bacteria, biofilm, prions and other infectiousagents.

Formulation embodiments disclosed herein are exposed to the bacterialand other pathogen structures that are desiccated by formulationembodiments disclosed herein. The structures desiccated include cellwall, plasma membrane, S-layers, glycocalyx, flagella, fimbriae andpili. Structures of both gram negative and gram positive bacteria aredesiccated and susceptible to destruction. While bacteria are described,it is understood that all microbes in a biofilm are susceptible todestruction by desiccation by a formulation embodiment disclosed herein.

Additionally, formulation embodiments disclosed herein prevent damagedone by a destructive inflammation immune response initiated bynecrotizing tissue by eliminating the necrotizing tissue before theresponse is prompted. Elimination of the necrotic tissue prevents thebody from initiating a destructive inflammatory immune response.

Formulation embodiments disclosed herein are effective for killingbacteria that are antibiotic resistant; such as MRSA. Formulationsdisclosed herein are also effective in killing bacteria that are in apersistent state. Bacteria in a persistent state are not completelyimmune to antibiotics but remain inactive or dormant in the presence ofantibiotic treatment. Once an antibiotic regime ends, the persistentbacteria resume their activity. Recent research identified the stimulusfor putting the bacteria into a persistent state which is attack by anantibiotic. The formulations disclosed herein are not conventionalantibiotics and when exposed to these formulation embodiments,antibiotic resistant bacteria and bacteria in a persistent state arekilled by desiccation before they enter a dormant or inactive state.

Formulation embodiments disclosed herein are also believed to killbacteria that have not been cultured in a lab. Bacteria that have notbeen cultured in a lab exist in nature but do not grow on laboratorymedia. At the present time, these bacteria are identified by theirunique genetic material. These bacteria are killed by desiccation in themanner disclosed herein.

Formulation embodiments that include free sulfuric acid have the freesulfuric acid component because sulfonation of the phenol and guaiacolor benzene performed does not remove residual sulfuric acid remaining atthe conclusion of the sulfonation reactions. In order to drive thesulfonation reaction to completion so that all of the phenol andguaiacol or benzene molecules become sulfonated, excess sulfuric acid isadded to a reaction mixture in a ratio of approximately 1:4:1phenolsulfonic acid to guaiacolsulfonic acid or benzenesulfonic acid tosulfuric acid so that there is an excess of sulfuric acid when thereaction is completed. The excess sulfuric acid is referred to as “freesulfuric acid” because it is not conjugated to a phenol or guaiacol.

The formulation embodiments that do not contain any free sulfuric acidare blended from a purified sulfonated aromatic that is obtained insulfonated form. Any residual or excess free sulfuric acid is removed,so that when blending is completed, there is substantially zero freesulfuric acid in the blend.

Specific liquid and gel formulations usable for treating wounds includethe following:

Formulation 1: Contains Free Acid in a Liquid Form

Phenolsulfonic acid—37% by weight

Guaiacolsulfonic acid—24% by weight

Free Sulfuric Acid—29% by weight

Water—10% by weight

Formulation 2: Contains Free Acid in a Gel Form Product Containing FreeAcid in the Gel Form

Phenolsulfonic acid—36% by weight

Guaiacolsulfonic acid—23% by weight

Free Sulfuric Acid—28% by weight

Water—10% by weight

Colloidal Silica—3% by weight

Formulation 3: Contains No Free Acid, in a Liquid Form

Product with No Free Acid in the Liquid Form

Benzenesulfonic acid—45% by weight

Phenolsulfonic acid—40% by weight

Water—15% by weight

Formulation 4: Contains No Free Acid, in a Gel Form

Product with No Free Acid in the Gel Form

Benzenesulfonic acid—43% by weight

Phenolsulfonic acid—38% by weight

Water—14% by weight

Colloidal Silica—5% by weight

Other formulation embodiments are disclosed below:

Formulation 5

Component Concentration Ranges Phenolsulfonic Acid 25-80% by weightGuaiacolsulfonic Acid 25-80% by weight Ammonium Phenolsulfonate  0-32%by weight Water 13-30% by weight

Formulation 6:

Component Concentration Ranges Phenolsulfonic Acid 25-80% by weightGuaiacolsulfonic Acid 25-80% by weight Ammonium Phenolsulfonate  0-5% byweight Water 13-30% by weightThe formulation is applicable to the wound as a liquid or as a gel.

While specific formulations have been disclosed, it has been found thatformulations having the following ranges are also suitable for use:

Formulation 7: Formulation Containing Free Acid (Percent by Weight)

Phenolsufonic acid (10-75% by weight)

Guaiacolsulfonic acid (10-75% by weight)

Free Sulfuric Acid (0-0.30% by weight)

Water (0-30% by weight)

Colloidal Silica (0-10% by weight)

Formulation 8:

Formulation with No Free Acid (Percent by Weight)

Benzenesulfonic acid (10-75% by weight)

Phenolsulfonic acid (10-75% by weight)

Water (0-30% by weight)

Colloidal Silica (0-10% by weight)

Other embodiments include method embodiments for treating chronicwounds. Chronic wounds include, but are not limited to chronic venousleg ulcers, pressure ulcers, diabetic ulcers, decubitus ulcers, stasisulcers, dermal ulcers, burns, and pressure ulcers. Chronic wounds arecharacterized by necrotic tissue that delays healing.

The method embodiments include applying a formulation embodimentdisclosed herein to the wound for 5 to 60 seconds. For some embodiments,a first debriding, such as mechanical debriding, is performed beforeadding the formulation embodiment. The method steps are repeated asappropriate. By “mechanically debride or mechanically debriding” ismeant that tissue at and around a wound that is lacerated or devitalizedor contaminated is removed with a mechanical device typically used insurgery such as a scissors or a scalpel or other surgical instrument.

For some embodiments, a single application of one of the formulationembodiments disclosed herein is performed. For some embodiments, themethod is performed once per day until the chronic wound is healed. Theterm, “chronic wound” as used herein, refers to wounds such as chronicvenous leg ulcers, pressure ulcers, diabetic ulcers, decubitus ulcers,stasis ulcers, dermal ulcers, burns, and pressure ulcers. Chronic woundsare characterized by necrotic tissue that delays healing and that doesnot heal within three months of onset.

In one exemplary embodiment, the formulation 6 disclosed herein wasapplied once to a chronic wound on the buttocks of a patient in a periodof three weeks. In this treatment example, shown in FIGS. 1-4, thesingle exposure of the chronic wound to the formulation embodimentresulted in the wound being healed three weeks after treatment, as shownin FIG. 4. In this example, the formulation 6 was not a el and wasapplied using a conventional tool. The formulation 6 was applied after adaily mechanical debridement.

The mechanical debridement includes scraping and excising tissue from awound in order to reach healthy, viable tissue. In some instances,debridement includes cutting through edges and base of a wound in orderto reach healthy tissue. The debridement is used with a scalpel, ringcurette, scissors and forceps.

Since the invention disclosed herein may be embodied in other specificforms without departing from the spirit or general characteristicsthereof, some of which forms have been indicated, the embodimentsdescribed herein are to be considered in all respects illustrative andnot restrictive. The scope of the invention is to be indicated by theappended claims, rather than by the foregoing description, and allchanges, which come within the meaning and range of equivalency of theclaims, are intended to be embraced therein.

1-41. (canceled)
 42. A method of treating a chronic wound, comprising: applying a formulation to the wound for 5 to 60 seconds, wherein the wound comprises broken skin, the formulation comprising: a formulation for treating chronic wounds, comprising: benzenesulfonic acid in a concentration of 10-75% wt. percent; phenolsulfonic acid in a concentration of 10-75% wt. percent]; water in a concentration of up to 30% wt. percent; and colloidal silica in a concentration up to 10% wt. percent wherein treating the chronic wound comprises reducing the size of the chronic wound.
 45. The method for treating the chronic wound of claim 42, wherein the chronic wound includes an infection by MRSA bacteria.
 46. The method for treating the chronic wound of claim 42, wherein the wound comprising broken skin is one or more of a chronic venous leg ulcer, diabetic ulcer, decubitus ulcer, stasis ulcer, dermal ulcer, burn or pressure ulcer.
 47. The method for treating the chronic wound of claim 42, further comprising debriding the chronic wound before applying the formulation to the wound.
 48. The method for treating a chronic wound of claim 42, wherein the formulation is applied to the wound as a single application.
 49. The method for treating a chronic wound of claim 42, wherein the formulation is applied once per day.
 50. A method for treating a chronic wound, comprising: Mechanically debriding the chronic wound; Applying a formulation to the wound for 5 to 60 seconds, the formulation consisting of: benzenesulfonic acid in a concentration of 10-75% wt. percent; phenolsulfonic acid in a concentration of 10-75% wt. percent]; water in a concentration of up to 30% wt. percent; and colloidal silica in a concentration up to 10% wt. percent wherein treating the chronic wound comprises reducing the size of the chronic wound. 